The cytokine Interleukin-10 (IL-10) is one of the most important immune suppressors which limits inflammation and enables a balanced nonpathogenic immune response. In order to identify IL-10-producing cells in vivo and ex vivo, respectively, an IL10-IRESEGFP-Reporter mouse was established. In this reporter mouse model EGFP-flourescence was only detectable in T cells. In order to achieve higher reporter sensitivity, several reporter constructs were generated and tested in cell culture system. Using IRES-mediated polycistronic reporter vectors it was shown, that reporter activity increases proportional to the number of IRES-EGFP-repeats. In addition it was shown that multiple IRES-EGFP-sequences did neither influence Cap-dependent translation nor posttranscriptional regulation by 3�-untranslated region (3�-UTR). To test the functionality of this IRES-mediated polycistronic reporter system in a transgenic mouse model, a targeting polycistronic reporter vector, IL10-3xIRESEGFP, was generated. This vector was integrated into the genome of the mouse embryonic stem cells (ES) by homologous recombination. The IL10-3xIRESEGFP-reporter mouse which will be established from already born chimeras will be investigated in further studies. To overcome the limits of reporter detection by the weak IL-10 promoter in a second approach we established a polycistronic reporter targeting vector by using ß-lactamase as reporter gene to generate an IL10-2xIRESBla-reporter mouse (IL10-Bla-mouse). This IL10-Bla-reporter mouse showed a strongly improved reporter activity. Under physiological conditions Bla-reporter activity could be detected in DCs, macrophages, B cells, T cells, NK cells and PMNs, in vitro and ex vivo. In addition the IL10-Bla-reporter mouse enables kinetic and real time expression studies. In contrast to the IL10-EGFP-reporter mice, Bla-reporter activity could be detected by in vivo infection studies in various cell types of the IL10-Bla-reporter mouse. On the basis of these results a model for the cellular expression profile of IL-10, called autocrine IL-10-dependent Regulation, was suggested and the obtained IL-10-Reporter results were discussed in this context.